The Endocrine System• This system is comprised of a variety of ductless glands. Some endocrine glands exist as discrete organs, while others are associated with exocrine glands and/or found within complex organs. All endocrine glands secrete their products (hormones) into the connective tissue surrounding the secretory elements; from there, those products enter the blood or lymph, in which they travel to their target organs.• While protein and steroid hormones differ in mechanism, the effects of both are mediated by specific receptors in their target cells.
Hypophysis (Pituitary Gland) General Structure• The hypophysis consists of both glandular and nervous portions. At low power, identify:• Pars anterior (2X, pars distalis; anterior pituitary).• Pars intermedia (2X, 5X).• Pars nervosa (2X, posterior pituitary).
Hypophysis (Pituitary Gland) Pars Distalis aka Pars Anterior• Anterior pituitary. Parenchymal cells can be divided into two classes on the basis of their staining characteristics: chromophils ("color-loving"), and chromophobes ("color- fearing"). Chromophils are further classified as acidophils and basophils.• Cells in this region produce numerous hormones (schematic), although each cell type produces only one type of hormone.• Note that the parenchyma consists of secretory epithelial cells arranged in anastomosing cords and clusters.• Note the abundant sinusoidal capillaries (20X, 40X) found here. What characteristics of sinusoidal capillaries make them appropriate here? fenestrations• Identify chromophobes (20X, 40X), and note their faintly- staining, sparse cytoplasm.• Identify acidophils (20X, 40X); note their strongly- staining, acidophilic cytoplasm. These cells are larger than chromophobes.• Identify basophils (20X, 40X).• Note that the cytoplasmic components primarily responsible for the staining characteristics of these cells are the secretory granules (40X).
Hypophysis (Pituitary Gland) Pars Intermedia• This intermediate portion of pituitary is part of the adenohypophysis, and thus is non-neural. It is composed of a thin layer of epithelial cells, some of which enclose colloid-filled spaces.• Identify colloid vesicles (10X), and the surrounding low columnar cells (10X, 40X, 40X).
Hypophysis (Pituitary Gland) Pars Nervosa• This portion is a downgrowth from the hypothalamus (schematic), and exhibits many characteristics of nervous tissue.• The axon terminals within this area originate from cells in the hypothalamus; those in the supraoptic nucleus produce ADH (vasopressin), while those in the paraventricular nuclei produce oxytocin (schematic).• Note that the cell bodies of these neurons are located in the hypothalamus, not the neurohypophysis. The pars nervosa contains no neuronal cell bodies.• Identify pituicytes (40X, 100X, 100X), which are glial cells.• Identify Herring bodies (40X, 100X, 100X, 100X). These are large axon terminals; they contain large numbers of neurosecretory granules.• Identify the rich capillary network present in pars nervosa (20X, 40X, 100X, 100X).
Thyroid Gland General Structure• This discrete endocrine gland is unique in that it stores the inactive form of hormone extracellularly in follicles (schematic).• General Structure. Identify the following:• Identify the connective tissue capsule (10X).• Identify connective tissue septa that divide the bilobed gland into lobules (10X).• Identify follicles (10X) of various sizes, all filled with pink-stained colloid and lined by cuboidal epithelial cells. These are the functional units of the thyroid gland. In general, follicle size varies inversely with secretory activity.
Thyroid Gland Thyroid Follicles• Identify the follicular epithelium (40X), which can vary from high cuboidal to low cuboidal (100X); this variability reflects the level of follicle secretory activity.• Note that follicle cells (100X) have large, centrally- or basally-located nuclei, and other characteristics that typify cells active in protein secretion. The storage and release of thyroid hormones involves the protein thyroglobulin (schematic).• Examine interfollicular regions (100X), and note the presence of connective tissue, sinusoidal capillaries (100X, into which hormone is released), and parafollicular cells (100X, see below).
Thyroid Gland Parafollicular Cells• Found scattered singly (40X, 40X) or in small groups (40X, 40X), these cells are responsible for production of thyrocalcitonin, a peptide hormone that is synthesized and secreted independently of thyroid hormone. These are also called C, clear, or light cells.• Note that parafollicular cells can be distinguished from follicular cells because they have eccentrically- placed nuclei and extensive, but lightly-stained, cytoplasm.
Parathyroid Glands General Structure• Two pairs of small parathyroid glands are in close anatomical association with the dorsal aspect of the thyroid gland (one pair for each thyroid lobe).General Structure• Identify the thin C.T. capsule (20X) that surrounds each gland and gives rise to internal septa (20X).• Note that parathyroid glands are actually embedded in the capsule of the thyroid gland.
Parathyroid Glands Parenchyma• Two types of epithelial cells comprise the parenchyma. They are present as a mass of crowded single cells, rather than arranged as follicles.Chief cells (principal cells). – Note the prominent nuclei, and the scant cytoplasmic staining of these cells (10X, 40X).Oxyphil cells. – Identify clumps of larger cells (10X, 40X) with rather acidophilic (oxyphilic) cytoplasm. Be aware that oxyphil cells are not always present in a section of parathyroid gland.
Parathyroid Glands Blood Supply• Examine the C.T. septa for blood vessels (10X) (and nerves), and note that, as with other endocrine glands, the parathyroid has a very rich vascular supply.• Look for capillaries among the parenchymal cells (100X).
Adrenal Glands General Structure• The adrenal (suprarenal) glands are closely applied to the cranial pole of each kidney. Like the pituitary, they are composed of two distinctly different components, one of mesothelial origin and one of neural origin (schematic).General Structure• Identify the outer cortex (2X), and the inner medulla (2X). These zones are readily observed even in a fresh, unstained section.• Identify the three histological zones (4X) of the cortex.• Identify the tough connective tissue capsule (20X) and radial trabeculae (20X) that extend into the cortex.• Look for the prominent central vein (4X, 20X) in the medulla.
Adrenal Glands Adrenal Cortex• The cortex is divided into three layers: – Zona glomerulosa reticularis – Zona fasciculata fasciculata – Zona reticularis glomerulosa medulla capsule
Adrenal Glands Adrenal Cortex: Zona Glomerulosa• Identify this outermost cortical layer (4X, 40X), and note the presence of columnar epithelial cells arranged in long cords (40X, 40X) that appear as ovoid clumps (50X) when cut in cross-section.• Note that the cytoplasm is basophilic and relatively scant (100X).• Note that capillary sinusoids (20X, 40X) are abundant.
Adrenal Glands Adrenal Cortex: Zona Fasciculata• Note that this is the broadest, lightest-staining of the three cortical zones, with epithelial cells (40X) that have large, abundant, poorly-stained cytoplasm.• Identify capillary sinusoids (20X, 40X) between cords of secretory cells.
Adrenal Glands Adrenal Cortex: Zona Reticularis• Note that the epithelial cells of this innermost, prominently stained zone are arranged in irregular, anastomosing cords and clumps (40X), with wide capillary sinuses intervening.• Note that the secretory cells (100X) are small, with relatively darkly stained cytoplasm that may contain yellow pigment.
Adrenal Glands Adrenal Medulla: Chromaffin Cells• Derived from neural crest, cells of the medulla are functionally equivalent to postganglionic sympathetic neurons.• Chromaffin cells. The secretory cells of the medulla contain catecholamines (norepinephrine and epinephrine) in cytoplasmic granules that are oxidized to a brown color by potassium bichromate (the chromaffin reaction). – Note that chromaffin cell cytoplasm (100X) is quite basophilic, compared to the acidophilia of the adjacent zona reticularis. – Note that the cells are arranged into tight clumps, with wide capillaries and venous channels intervening (40X, 100X).
Adrenal Glands Adrenal Medulla: Blood Supply• The medullary capillary network receives blood from a capsular plexus both indirectly, via cortical capillary sinusoids, and directly, via small arteries passing through the cortex from the capsule (schematic).• Identify the extensive network of dilated capillaries (40X, 100X) in the medulla.
Epiphysis (Pineal Gland) General Structure• The pineal gland (2X) is an evagination of the diencephalon of the brain, and contains highly modified neurons called pinealocytes.General structure• Under low power, identify trabeculae that arise from pia mater. Trabeculae divide the pineal parenchyma into indistinct lobules.
Epiphysis (Pineal Gland) Parenchyma• The parenchyma contains two cell types, pinealocytes and neuroglia. The pinealocytes are modified neurons. You will not need to distinguish these two cell types.
Epiphysis (Pineal Gland) Pineal Sand• Identify these basophilic, extracellular concretions (10X). They are often calcified, which makes the pineal gland an excellent radiological marker, particularly of the midline.
Epiphysis (Pineal Gland) Blood Supply and Innervation• The pineal is innervated by unmyelinated axons of postganglionic sympathetic neurons. This is an unusual example of a central nervous system structure that receives sympathetic innervation.• Note the presence of a rich vascular supply (100X, 20X), characteristic of all endocrine glands.• What principal type of information does the pineal receive?
Endocrine Pancreas: Islets of Langerhans• The pancreas is a mixed exocrine and endocrine gland. The overall structure and both exocrine and endocrine portions of the pancreas have been studied in the laboratory session on the digestive system.General Structure• Note that islet cells are found as clumps of small secretory cells (1X, 10X, 10X, 20X, 40X, 40X,) with relatively lightly-stained cytoplasm (100X).• Compare their appearance to that of the prolific protein-secreting cells of exocrine pancreatic acini (40X, 50X, 100X).• Identify the rich network of capillaries (40X) that characterize all endocrine organs.
Clinical Correlation1. Goiter (Multinodular) Multinodular goiter is a common cause of overactivity of the thyroid gland (hyperthyroidism). A mutation in the gene coding for the TSH receptor prevents the follicular cells from responding to TSH; instead, they produce thyroid hormones constitutively (i.e. all the time). The increased hormone production results in the formation of characteristic large nodules (low mag, 1X). The condition may be treated by surgical removal of part of the thyroid, or by injection of radioactive iodine, which kills the surrounding thyroid tissue.2. 2. Hashimotos Thyroiditis This is an autoimmune condition in which the immune system attacks the thyroid, causing a dramatic reduction in the number and size of follicles. It is treated by replacement administration of thyroid hormone. The autoimmune nature of the condition is apparent from the large number of lymphocytes within the organ (low mag, 10X).
Pathology• Adrenal Atrophy: – You see hypoplasia (decrease in cells) usually in the cortex but also gaps in the medulla – Proliferation of parenchymal cells• Adrenal Pheochromocytoma: – Medulla is enlarged and represents the majority of the adrenal gland (whereas in a healthy adrenal gland, the cortex is the majority of tissue) – Almost always benign – Large, bizarre looking nuclei (large and dark-staining) – Large vascular spaces• Hyperparathyroidism (bone): – Within the bone spicules, you can see osteoclasts degrading the bone (more osteoclasts than usual) – Recall that osteoclasts are multinucleate• Type II Diabetes (pancreas): – Enlarged islets of Langerhans – Hyaline deposits in the islets (pinker than usual)
Pathology (cont.)• Parathyroid Oxyphil Adenoma: – Identify healthy parathyroid for its darkly staining chief cells, pink oxyphil cells, and fat throughout – The area with tumor is made entirely of oxyphil cells (less chief cells) – Monoclonal proliferation= tumor composed of 1 type of cell• Pituitary Acidophilic Adenoma: – Tumors tend to be in the anterior pituitary; monoclonal proliferations of 1 of the 3 common anterior pituitary cells – In this case, it is an acidophilic adenoma so the cytoplasms are predominantly pink-staining – Acidophils make hormones that serve non-endocrine glands (ex. Mammary gland)• Graves Disease (hyperthyroid): – Follicles are very small (little colloid) – Colloid appears to have open spaces along its edge scalloped edges (common to hyperthyroidism)• Hashimoto’s Thyroiditis(hypothyroid): – Autoimmune disease against thyroid – Lymphoid follicles (darkly stained clusters) seen throughout the thyroid – Follicles are smaller than usual